Preeclampsia is a syndrome characterized by the development of hypertension and proteinuria in the third trimester of pregnancy. It is responsible for 6% of premature births and is the second leading cause of maternal mortality. Gant et al, by measuring angiotension sensitivity and dehydroisoandrosterone clearance, demonstrated that pathophysiological changes occur weeks prior to the manifestation of clinical hypertension. Increased systemic vascular resistance is thought to be associated with these early changes and eventually leads to hypertension. However, hemodynamic measurements late in the disease reveal a diversity of findings with a significant number of patients having elevated cardiac output and normal systemic vascular resistance. The heterogeneity of findings suggest that preeclampsia may be a dynamic process requiring a longitudinal design for study. Our preliminary data support a hypothesis that the primary hemodynamic alteration early in the disease is elevated CO. The goals of the projects are to define the longitudinal hemodynamic changes in women destined to become preeclamptic. We will test the hypothesis that early preeclampsia is manifest by increased CO which is followed by hypertension. One hundred and seventy nulliparous women will be studied over three years. Cardiac output, blood pressure and weight will be measured at regular intervals starting before 22 weeks. At the conclusion of each pregnancy, subjects will be classified as normotensive, hypertensive without protenuria or preeclamptic. Data from the preeclamptic and hypertensive patients will be compared with those who remain normotensive. An understanding of the longitudinal hemodynamic changes in preeclampsia will serve as the foundation of further research into a common disease process which is associated with significant morbidity. It may aid in the detection of incipient preeclampsia, suggest preventive therapy, and help direct the treatment of women with overt disease.